The proposed research will combine virologic, light and electron microscopic as well as immunofluorescence methods to study in vivo and in vitro demyelination caused by viruses. (1) Studies of JHM virus-induced demyelination will continue in attempts to produce chronic infection and to further clarify the mechanisms of disease in animals and organ cultures. (2) The recent virus isolates from progressive multifocal leukoencephalopathy (PML) will be further characterized and attempts will be made to experimentally produce disease in small laboratory animals and primates. (3) Attempts will be made to isolate viruses from selected human biopsy and autopsy tissue utilizing in vitro methods similar to those employed in the isolation of the PML viruses.